The combination of iberdomide and dexamethasone demonstrated “meaningful” clinical activity in a phase 1/2 trial of patients with relapsed or refractory multiple myeloma, researchers reported in The Lancet Haematology.

This phase 1/2 trial (ClinicalTrials.gov Identifier: NCT02773030) enrolled MM patients who were 18 years of age or older and had received at least 2 previous lines of therapy, including lenalidomide or pomalidomide and a proteasome inhibitor.

Iberdomide was given in escalating doses (0.3-1.6 mg on days 1-21 of each 28-day cycle) in combination with dexamethasone (40 mg [20 mg if >75 years] once per week).


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There were 90 patients in the dose-escalation cohort and 107 in the dose-expansion cohort. The median follow-up was 5.8 months in the dose-escalation cohort and 7.7 months in the dose-expansion cohort. 

The maximum tolerated dose was not reached, although 2 dose-limiting toxicities occurred, both in the dose-escalation cohort. Both were infections and occurred at the 1.2 mg and 1.3 mg doses. The recommended phase 2 dose of iberdomide was 1.6 mg. 

The overall response rate in the dose-escalation cohort was 32%, and the median duration of response was 10.4 months. One patient had a complete response, 8 had a very good partial response, and 20 had a partial response. The rate of stable disease was 36% (n=32). 

In the dose-expansion cohort, the overall response rate was 26%. One patient had a stringent complete response, 8 had a very good partial response, and 19 had a partial response. The rate of stable disease was 43% (n=46). 

The median duration of response was 7.0 months in the dose-expansion cohort. The median progression-free survival in this group was 3.0 months, and the median overall survival was 10.7 months.

In the dose-escalation cohort, 53% of patients experienced a serious treatment-emergent adverse event (TEAE), and 6 patients discontinued iberdomide for this reason. The most common grade 3 or higher TEAEs were neutropenia (42%), anemia (27%), and infection (26%).

In the dose-expansion cohort, 53% of patients experienced a serious TEAE, 5 patients discontinued iberdomide due to TEAEs, and there was 1 treatment-related death (due to abdominal sepsis). Grade 3 or higher TEAEs occurred in 82% of patients in the dose-expansion cohort. The most common were neutropenia (45%), anemia (28%), infection (27%), thrombocytopenia (22%), and leukopenia (21%). 

“Iberdomide plus dexamethasone was generally safe and showed meaningful clinical activity in heavily pretreated patients with multiple myeloma, including in disease that was refractory to immunomodulatory drugs,” the researchers concluded. “These data suggest that further evaluation of iberdomide plus dexamethasone or other standard antimyeloma therapies is warranted.”

Disclosures: This research was supported by Celgene, a Bristol Myers Squibb company. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Lonial S, Popat R, Hulin C, et al. Iberdomide plus dexamethasone in heavily pretreated late-line relapsed or refractory multiple myeloma (CC-220-MM-001): A multicentre, multicohort, open-label, phase 1/2 trial. Lancet Haematol. Published online October 6, 2022. doi:10.1016/S2352-3026(22)00290-3